Epidemiology and Evolution of Invasive Pneumococcal Disease Caused by Multidrug Resistant Serotypes of 19A in the 8 Years After Implementation of Pneumococcal Conjugate Vaccine Immunization in Dallas, Texas

Department of Pediatrics, Division of Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
The Pediatric Infectious Disease Journal (Impact Factor: 2.72). 11/2009; 29(4):294-300. DOI: 10.1097/INF.0b013e3181c2a229
Source: PubMed


The heptavalent pneumococcal conjugate vaccine (PCV7) has significantly reduced vaccine-type invasive pneumococcal disease (IPD) in children. An increasing percentage of IPD cases are now caused by nonvaccine serotypes. The purpose of our observational study was to define the epidemiology of pneumococcal disease in Dallas, TX children for 8 years after implementation of PCV7 immunization.
Streptococcus pneumoniae isolates from normally sterile sites were collected at Children's Medical Center of Dallas from January 1, 1999 to December 31, 2008. Incidence of IPD was calculated using inpatient and emergency center admissions to Children's Medical Center of Dallas as the denominator. Isolates were serotyped and penicillin and cefotaxime susceptibilities were determined. Serotype 19A isolates were further characterized by multilocus sequence typing.
Compared with the prevaccine period of 1999-2000, there was a significant reduction in the incidence of IPD from 2002 to 2008 (P < 0.05), although a significant increase in IPD incidence was observed from 2006 to 2008 (P = 0.038). The number of IPD cases caused by serotype 19A increased from 1999 to 2008 (P < 0.001). There were significant increases in penicillin and cefotaxime nonsusceptible 19A isolates during this 10-year period (P < 0.001 and P = 0.004, respectively). The most common sequence type (ST) of the 19A isolates was ST-199 (42.7%). Clonal complex (cc-156) and cc-320 emerged in the period of 2005-2008 as penicillin and cefotaxime resistant 19A strains.
In Dallas, PCV7 immunization reduced significantly the incidence of IPD caused by vaccine-type strains. A significant increase in IPD caused by serotype 19A was observed. The penicillin and cefotaxime nonsusceptible STs, not previously identified in Dallas, have recently become an important cause of IPD.

9 Reads
  • Source
    • "Studies conducted after PCV7 introduction, have shown dramatic and sustained decreases in vaccine type (VT) IPD rates, carriage and herd effects [10-13]. These positive findings were followed by reports of IPD caused by non vaccine types (NVT) S. pneumoniae PNSP and MDR [14-18]. NVT have also been described as agents of non invasive disease [15] and nasopharyngeal carriage [12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Pneumococcal conjugate vaccines (PCVs) are in the process of implementation in Latin America. Experience in developed countries has shown that they reduce the incidence of invasive and non-invasive disease. However, there is evidence that the introduction of PCVs in universal mass vaccination programs, combined with inappropriate and extensive use of antibiotics, could be associated to changes in non-PCV serotypes, including serotype 19A. We conducted a systematic review to determine the distribution of serotype 19A, burden of pneumococcal disease and antibiotic resistance in the region. We performed a systematic review of serotype 19A data from observational and randomized clinical studies in the region, conducted between 1990 and 2010, for children under 6 years. Pooled prevalence estimates from surveillance activities with confidence intervals were calculated. We included 100 studies in 22 countries and extracted data from 63. These data reported 19733 serotyped invasive pneumococcal isolates, 3.8% of which were serotype 19A. Serotype 19A isolates were responsible for 2.4% acute otitis media episodes, and accounted for 4.1% and 4.4% of 4,380 nasopharyngeal isolates from healthy children and in hospital-based/sick children, respectively. This serotype was stable over the twenty years of surveillance in the region. A total of 53.7% Spn19A isolates from meningitis cases and only 14% from non meningitis were resistant to penicillin. Before widespread PCV implementation in this region, serotype 19A was responsible for a relatively small number of pneumococcal disease cases. With increased use of PCVs and a greater number of serotypes included, monitoring S. pneumoniae serotype distribution will be essential for understanding the epidemiology of pneumococcal disease.
    BMC Infectious Diseases 05/2012; 12:124. DOI:10.1186/1471-2334-12-124 · 2.61 Impact Factor
  • Source
    • "Pneumococcal serotypes are defined by the chemical structure of the capsular polysaccharides, and pneumococcal serogroups consist of structurally related serotypes that in some cases share some immunological cross-reactivity. However, crossfunctional responses, as defined by the opsonophagocytic activity (OPA) assay, and crossprotection provided by immune responses to related serotypes may vary between individual serotypes within serogroups While strong immunological cross-reactivity by ELISA has been demonstrated in some cases, e.g., serotypes 19A and 19F, little cross-functional activity in OPA assays and no evidence of cross-protection has been observed in human populations for these two related serotypes [9] [10] [11] [12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 dramatically reduced the incidence of invasive pneumococcal disease (IPD) caused by the seven serotypes covered by the vaccine. Following the introduction of PCV7, which contains a serotype 6B conjugate, some decrease in IPD due to serotype 6A was noted suggesting that the serotype 6B conjugate provided some partial cross-protection against serotype 6A. However, no effect on serotype 6C was observed. In 2010, a pneumococcal conjugate vaccine with expanded serotype coverage (PCV13) was introduced that expanded the serotype coverage to 13 serotypes including serotype 6A. To assess whether the 6A conjugate in PCV13 could potentially induce functional anti-6C antibody responses, an opsonophagocytic assay (OPA) for serotype 6C was developed. Randomly chosen subsets of immune sera collected from infants receiving three doses of PCV7 or PCV13 were tested in OPA assays for serotype 6A, 6B and 6C. PCV7 immune sera demonstrated strong OPA responses, defined as percentage of subjects having an OPA titer ≥1:8, to serotype 6B (100% responders), partial responses to serotype 6A (70% responders) but only minimal responses to serotype 6C (22% responders). In contrast, PCV13 immune sera showed strong OPA responses to serotypes 6A (100% responders), 6B (100% responders) and 6C (96% responders). Furthermore, during pre-clinical work it was observed that serotype 7F (included in PCV13) and serotype 7A (not included in PCV13) shared serogroup-specific epitopes. To determine whether such epitopes also may be eliciting cross-functional antibody, PCV13 immune sera were also tested in serotype 7A and 7F OPA assays. All PCV13 immune sera demonstrated OPA responses to both of these serotypes. Taken together these results suggest that immunization with PCV13 has the potential to induce cross-protective responses to related serotypes not directly covered by the vaccine.
    Vaccine 06/2011; 29(41):7207-11. DOI:10.1016/j.vaccine.2011.06.056 · 3.62 Impact Factor
  • Source
    • "All three clones have persisted into the post-vaccine population with a new serotype not targeted by the vaccine, and in each the predominant serotype is 19A. The most successful and clinically significant is ST 320 (Beall et al., 2006; Beall et al., 2011; Brueggemann et al., 2007; Pai et al., 2005b; Pelton et al., 2007; Techasaensiri et al., 2010), which is a close relative of ST 236, Taiwan 19F -14. In addition to an important role in invasive pneumococcal disease (IPD), ST 320 is increasingly common in carriage (unpublished observations). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Infections caused by multiresistant Gram-positive bacteria represent a major health burden in the community as well as in hospitalized patients. Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium are well-known pathogens of hospitalized patients, frequently linked with resistance against multiple antibiotics, compromising effective therapy. Streptococcus pneumoniae and Streptococcus pyogenes are important pathogens in the community and S. aureus has recently emerged as an important community-acquired pathogen. Population genetic studies reveal that recombination prevails as a driving force of genetic diversity in E. faecium, E. faecalis, S. pneumoniae and S. pyogenes, and thus, these species are weakly clonal. Although recombination has a relatively modest role driving the genetic variation of the core genome of S. aureus, the horizontal acquisition of resistance and virulence genes plays a key role in the emergence of new clinically relevant clones in this species. In this review, we discuss the population genetics of E. faecium, E. faecalis, S. pneumoniae, S. pyogenes and S. aureus. Knowledge of the population structure of these pathogens is not only highly relevant for (molecular) epidemiological research but also for identifying the genetic variation that underlies changes in clinical behaviour, to improve our understanding of the pathogenic behaviour of particular clones and to identify novel targets for vaccines or immunotherapy.
    FEMS microbiology reviews 06/2011; 35(5):872-900. DOI:10.1111/j.1574-6976.2011.00284.x · 13.24 Impact Factor
Show more